16-635672-C-G

Position:

• chr16-635672-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032366.5(METTL26):​c.300G>C​(p.Gln100His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: METTL26 NM_032366.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.385

Genes affected

METTL26 (HGNC:14141): (methyltransferase like 26)

METTL26 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10807362).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
METTL26	NM_032366.5	c.300G>C	p.Gln100His	missense_variant	2/6	ENST00000301686.13	NP_115742.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
METTL26	ENST00000301686.13	c.300G>C	p.Gln100His	missense_variant	2/6	2	NM_032366.5	ENSP00000445926.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 21, 2021

The c.300G>C (p.Q100H) alteration is located in exon 2 (coding exon 2) of the METTL26 gene. This alteration results from a G to C substitution at nucleotide position 300, causing the glutamine (Q) at amino acid position 100 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	T;.;T;.;.;.
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.64	T;T;T;T;T;T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.11	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
PROVEAN	Benign	-1.4	.;N;N;N;N;N
REVEL	Benign	0.0080
Sift	Benign	0.18	.;T;T;T;T;T
Sift4G	Benign	0.086	T;T;T;T;.;T
Polyphen		0.0010	.;.;B;.;.;.
Vest4		0.081
MutPred		0.46		Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);.;Loss of helix (P = 0.1706);
MVP		0.14
MPC		0.028
ClinPred		0.50	D
GERP RS		0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.071
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2037120569; hg19: chr16-685672;